Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several lines of evidence have implicated acetylcholine (ACh) as one of the neurotransmitters found to be decreased in Alzheimer's disease (AD). Various methods of cholinergic augmentation have been attempted, with mixed results. Tetrahydroaminoacridine (THA), an acetylcholinesterase inhibitor, is currently being investigated at the McGill Centre for Studies in Aging. Preliminary uncontrolled data from a 10-week clinical trial of THA and lecithin, reported elsewhere, suggest a clinically modest but statistically significant beneficial effect on cognition, although problems exist with side effects, particularly gastrointestinal. Since the suggestion by Janowsky in 1972 that cholinergic neurotransmission may exert an inhibitory or depressant effect on mood, the evidence accumulated in the literature has been inconclusive. We undertook to assess several potential pretreatment correlates of depressive symptoms in AD and to monitor the course of these symptoms during the 10 week treatment period, using the Geriatric Depression Scale (GDS) of Brink and Yesavage. Pretreatment GDS scores were found to correlate with degree of overall disability and dementia as measured by the Rapid Disability Rating Scale (RDRS) and the Mini Mental State Examination (MMS), respectively. GDS scores over the treatment period did not change to a statistically significant degree. The meaning of these results is discussed, particularly with reference to the difficulty of diagnosis and measurement of depression in the setting of dementia.
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PMID:Canadian collaborative study of tetrahydroaminoacridine (THA) and lecithin treatment of Alzheimer's disease: effect on mood. 265 61

Many of the drugs used in anesthesia and intensive care may cause blockade of the central cholinergic neurotransmission. Acetylcholine is of significance in modulation of the interaction among most other central transmitters. The clinical picture of the central cholinergic blockade, known as the central anticholinergic syndrome (CAS), is identical with the central symptoms of atropine intoxication. This behaviour consists of agitation including seizures, restlessness, hallucinations, disorientation or signs of depression such as stupor, coma and respiratory depression. Such disturbances may be induced by opiates, benzodiazepines, phenothiazines, butyrophenones, ketamine, etomidate, propofol, nitrous oxide, and halogenated inhalation anesthetics as well as by H2-blocking agents such as cimetidine. There is an individual predisposition for CAS--but unpredictable from laboratory findings or other signs. Reports of postanesthetic occurrence of the CAS requiring treatment are not unanimous, varying between 1 and 40%. Differential diagnosis of the CAS includes disorders of glucose and electrolyte metabolism, severe hormonal imbalance, respiratory disorders (hypoxia, hypercarbia), hypothermia, hyperthermia and neuropsychiatric diseases (cerebral hypoxia, stroke, catatony, acute psychosis). The CAS may considerably impair the postanesthetic period especially when agitation is prevalent, which may endanger the patient or the surgical results. The diagnosis is confirmed ex iuvantibus by the sudden increase in the acetylcholine level in the brain. This is achieved with physostigmine, a cholinesterase inhibitor able to easily cross the blood-brain barrier. Its peripheral muscarinic effects are minimal. Postanesthetic CAS can be prevented by administration of physostigmine during the anesthesia procedure. During intensive care (IC), agitated forms of CAS may occur in patients undergoing mechanical ventilation, particularly during prolonged high-dose sedation. Artificial ventilation of such patients becomes very difficult and muscle relaxation may be necessary. In these cases of IC-CAS, physostigmine is of value and has proven beneficial during weaning from mechanical ventilation. Dealing with the CAS for more than a decade has improved knowledge of the central cholinergic transmission. For example, it can be said that CAS occurs alongside general anesthesia, being no more than a frequent side-effect. Furthermore, acetylcholine is involved in nociception through the endorphinergic and the serotoninergic systems. There is a close relation between the central cholinergic transmission and actions of nitrous oxide. Moreover, cholinergic transmission is involved in withdrawal from (among others) alcohol, opiates, hallucinogens and nitrous oxide. In some intoxications with psychoactive agents, physostigmine is useful for reversal of the central nervous symptoms of the acute intoxication itself. In addition it can be used for prevention of some withdrawal states. In
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PMID:Central anticholinergic syndrome (CAS) in anesthesia and intensive care. 268 49

In high spinal cats, the acute time-dependent changes of both the activity of spinal reflex pathways and the activity of three different esterases (acetylcholinesterase, carboxylesterase and neurotoxicant target enzyme) in the spinal cord were investigated after intravenous application of the organophosphorus compound di-isopropyl phosphofluoridate (DFP). There is no general depression of spinal reflexes by DFP. While the recurrent inhibition is completely abolished for a long time and the reflexes to a flexor (PBSt) are depressed but with a shorter recovery time, the reflexes to an extensor (GS) are distinctly less depressed or even facilitated. Reflex pathways from skin afferents to motoneurones did not react in a uniform way to DFP, e.g. inhibitory nociceptive pathways were less affected than excitatory ones. Esterase activities were heavily depressed and recovered with different time courses. The acute DFP action cannot be explained by a uniform intoxication of all spinal functions but probably emerges from a differential action on different interneuronal systems.
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PMID:Influence of the organophosphorus compound DFP on inhibitory motor systems and esterase activity in the spinal cord of cats. 271 Apr 27

Five incidences of bird mortality in Georgia and West Virginia (USA) involving migratory waterfowl, cranes, raptors, corvids and songbirds were investigated during the first 6 mo of 1988. Gross and histopathologic examinations revealed no evidence of infectious or other diseases. However, severe depression of cholinesterase activity was evident in brains of birds found dead, suggesting gross exposure to an organophosphorus (OP) or carbamate pesticide. All of the gastrointestinal tract contents chemically analyzed contained famphur, an OP insecticide used as a pour-on treatment against lice and grubs on livestock, ranging from 5 to 1,480 ppm (wet weight). Grain scattered at two of the mortality sites contained 4,240 and 8,500 ppm famphur. Gastrointestinal tracts of most of the dead birds contained mainly corn and some wheat. This is the first report to document the use of famphur as an intentional means of killing wildlife thought to be depredating crops.
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PMID:Case histories of wild birds killed intentionally with famphur in Georgia and West Virginia. 271 98

The ability of physostigmine (PHY) and pyridostigmine (PYR) to protect against the segmental synaptic depression caused by sarin was examined in isolated spinal cords from neonatal rats. The monosynaptic reflex was unaffected at concentrations up to 0.1 microM PHY or 0.3 microM PYR but raising the concentrations of either drug produced a concentration-dependent depression of the monosynaptic reflex which could be completely antagonized by atropine. The monosynaptic reflex was depressed by 50% at 0.45 microM PHY and 2 microM PYR with maximal depression occurring at 1 microM PHY (to about 10% of control) and 10 microM PYR (to about 35% of control). Pretreating the cords with 0.1 microM PHY and PYR for 30 min failed to protect against the depressant effects of sarin even though they inhibited total cholinesterase (ChE) by 27 and 21%, respectively. Both PHY and PYR depressed total ChE activity of the spinal cord in a concentration-dependent manner with 50% inhibition of ChE occurring at 0.8 microM. These results suggest that the carbamates affect segmental transmission by activation of a muscarinic receptor, that protective carbamylation of ChE is ineffective against organophosphorus-induced segmental depression, and that inhibition of ChE is unrelated to both carbamate- and organophosphorus-induced depression of the monosynaptic reflex.
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PMID:Interaction of reversible and irreversible cholinesterase inhibitors on the monosynaptic reflex in neonatal rats. 272 98

We have studied the action of doxapram on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation. Doxapram augmented neuromuscular transmission in a dose-related manner when a threshold concentration of 5 x 10(-5) mol litre-1 had been exceeded. The activity of the acetylcholinesterase in rat diaphragm has been examined also in the presence of doxapram. No inhibitory effect was seen in the concentration range which augmented neuromuscular transmission, thus excluding cholinesterase inhibition as the underlying mechanism. In contrast, in the presence of partial neuromuscular block, a dose-related depression of neuromuscular transmission with doxapram was revealed. This was greatest when the neuromuscular blocking agents possessed significant presynaptic activity (beta-bungarotoxin and tubocurarine). In this situation any facilitatory action of doxapram was severely reduced or abolished. In contrast, the facilitatory effects of doxapram were apparent in the presence of partial block produced by agents with less or no presynaptic activity (pancuronium and alpha-bungarotoxin). This study suggests that doxapram has a presynaptic facilitatory action at the neuromuscular junction. In the presence of partial neuromuscular block, an inhibitory action is revealed which may be post-junctional. The concentrations of doxapram at which these effects appear are approximately five times greater than those reached in plasma after a standard clinical dose.
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PMID:Doxapram and the neuromuscular junction. 231 31

Exogenously applied muscarinic agonists--for example, acetylcholine (ACh) and acetyl-beta-methacholine (MCh)--modify frequency receptive fields in auditory cortex of unanesthetized animals in a frequency-specific rather than global manner. The present study sought to relate these findings to endogenous actions of ACh by using the anticholinesterase agents eserine sulphate and soman (0-1,2,2-trimethylpropylmethylphosphonofluoridate) to facilitate the effects of endogenous ACh. Frequency receptive fields (FRF) were determined by presenting sequences of different isointensity tones before, during, and after application of ACh, MCh, eserine, or soman; also the cholinesterase blockers were applied between applications of ACh or MCh. The major effects produced by the inhibitors were similar to those of the agonists. Predominant effects were frequency-specific changes in FRF. Further, eserine and soman, similar to ACh and MCh, produced shifts in the best frequency (BF) of FRF due mainly to coordinated depression of responses to the BF and increased responses to adjacent, non-BF. The results indicate that exogenous and endogenous ACh, acting via muscarinic receptors, can significantly influence the physiological functioning of cortical neurons and consequently their processing of sensory information.
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PMID:Cholinergic modulation of frequency receptive fields in auditory cortex: II. Frequency-specific effects of anticholinesterases provide evidence for a modulatory action of endogenous ACh. 277 38

Episodes of tachycardia induced by strong vagal stimulation in spontaneously beating isolated atria of frog (Rana temporaria) were studied with multielectrode mapping technique. These episodes were inducible in 19 of 39 preparations. The arrhythmia started several seconds after cessation of vagal stimulation strong enough to cause sinus arrest, without electrical stimulation of the myocardium. The arrhythmia consisted of two to 20 beats (6 +/- 4, mean +/- SD, n = 42) with a cycle length of 100-500 msec. Recording from 32 sites with spatial resolution of 1-2 mm showed that the arrhythmia was due to intra-atrial circus movement. The estimated perimeter of the reentrant circuit ranged from 6 to 20 mm. In circuits of the minimal size, the average conduction velocity along the circuit was as low as 2-3 cm/sec. Paroxysms of the tachycardia were always preceded by vagally induced nonuniform depression of conduction, with some areas of atria being completely blocked. As the vagal influence decreased, the blocked areas recovered in an inhomogeneous manner, their unblocking being significantly (p less than 0.05) delayed after inhibition of tissue cholinesterase by proserine. The reentrant tachycardia was initiated when a sinus impulse arrived during certain phase of the unblocking. Unlike the well-known mechanism of reentrant excitation, which is based on inhomogeneous refractoriness and critically timed extrabeat(s), the circus movement in our model depended on vagally induced conduction block and could be launched by a single sinus impulse.
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PMID:Vagally induced block and delayed conduction as a mechanism for circus movement tachycardia in frog atria. 278 63

Postsynaptic effects of vinblastine (VB) and colchicine (CCH) were studied in the frog neuromuscular junction under voltage-clamp conditions. The same concentrations of VB and CCM, which did not affect the amplitude and duration of miniature end plate currents (MEPC), the current-voltage relationship of peak end plate currents (EPC) and voltage sensitivity of the decay phase of EPC, markedly reduced the responses to iontophoretic application of acetylcholine. Both VB and CCH accelerated the EPC decay when acetylcholinesterase was inhibited; they also caused a pronounced depression in the trains of EPC (10 Hz) and trains of responses to acetylcholine application (5-10 Hz). It was concluded that use-dependent effects of VB and CCH are not connected with their influence on the cytoskeleton of the muscle fibre, but can be a result of accelerated desensitization of cholinoreceptors.
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PMID:[Effect of vinblastine and colchicine on the postsynaptic membrane of the myoneural junction in the frog]. 283 69

The organophosphorus compounds diisopropylphosphorofluoridate (DFP) and isopropylmethylphosphonofluoridate (sarin) depressed the monosynaptic reflex (MSR) in spinal cords from 7- to 9-day-old male rats. The concentrations of DFP and sarin which depressed the MSR by nearly 50% were 100 microM and 100 nM, respectively. Simultaneous superfusion of the cords with thyrotropin-releasing hormone (TRH) with either DFP or sarin resulted in a reversal of the depression. The depression caused by DFP was reversed to 95% of control by 100 nM TRH whereas similar reversal of sarin-induced depression required a 10-fold greater concentration of TRH. The potentiating effect of TRH was not affected by atropine even at a high concentration (1 microM) although atropine easily reversed organophosphorus-induced depression of the MSR. It appears that reversal of organophosphorus-induced depression by TRH might occur through a noncholinergic, TRH-sensitive receptor mechanism and may be unrelated to acetylcholinesterase activity. This action represents a possible utility of TRH as an adjunct in organophosphorus toxicity.
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PMID:Segmental synaptic depression caused by diisopropylphosphorofluoridate and sarin is reversed by thyrotropin-releasing hormone in the neonatal rat spinal cord. 284 64


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